Method of treatment and prophylaxis of diseases related to amyloid deposition using IgM

Abstract

The invention relates to a method of treating or preventing disease associated with β-amyloid polypeptides comprising administration of an immunoglobulin preparation enriched in immunoglobulin M (IgM), and pharmaceutical compositions comprising such preparations.

The invention claimed is: 
     
       1. A method for preparing an immunoglobulin preparation comprising immunoglobulin M (IgM) molecules that specifically bind Aβ1-42 peptides from pooled human plasma comprising:
 (a) performing a first caprylate precipitation such that a first precipitate and a first supernatant comprising immunoglobulins are formed; 
 (b) separating the first supernatant from the first precipitate; 
 (c) performing a second caprylate precipitation such that a second precipitate and a second supernatant comprising immunoglobulins are formed; 
 (d) separating the second supernatant from the second precipitate; 
 (e) contacting the second supernatant with a first anion exchange resin; 
 (f) separating a fraction containing substantially all of the immunoglobulin G and immunoglobulin M from the result of step (e); 
 (g) contacting the fraction of step (f) with a second anion exchange resin; 
 (h) eluting IgM from the second anion exchange resin column; 
 (i) applying the IgM to a gel filtration resin and recovering the IgM; 
 (j) applying the IgM to an affinity resin comprising immobilized antigens A and B; and 
 (k) recovering the eluted IgM to obtain a purified, virally inactivated IgM preparation. 
 
     
     
       2. The method of  claim 1 , wherein the immunoglobulin preparation comprises at least about 80% IgM or at least about 90% IgM. 
     
     
       3. The method of  claim 1 , wherein the IgM has a titer of specific binding for an Aβ1-42 peptide that is at least 10-times higher than that for an Aβ1-40 peptide. 
     
     
       4. The method of  claim 1 , wherein the immunoglobulin preparation comprises less than 5% oligomeric IgM. 
     
     
       5. The method of  claim 1 , wherein the IgM is a monomeric or proteolytic fragment of IgM that specifically binds an Aβ1-42 peptide. 
     
     
       6. The method of  claim 1 , further comprising:
 (a) identifying a patient having an increased risk of developing or showing symptoms of a disease associated with β-amyloid polypeptides; and 
 (b) administering to the patient an effective amount of the immunoglobulin preparation. 
 
     
     
       7. The method of  claim 6 , wherein the effective amount is about 0.1 μg per kg body weight to about 1000 mg per kg body weight. 
     
     
       8. The method of  claim 6 , wherein the effective amount is about 0.5 μg per kg body weight to about 500 mg per kg body weight; about 0.5 μg per kg body weight to about 100 mg per kg body weight; or about 5 μg per kg body weight to about 50 mg per kg body weight. 
     
     
       9. The method of  claim 6 , wherein the step of administering comprises administering by a parenteral route. 
     
     
       10. The method of  claim 6 , wherein the disease associated with β-amyloid polypeptides in a patient is selected from the group consisting of systemic senile amyloidosis, familial amyloid polynephropathy (Iowa), familial amyloidosis (Finnish), Gerstmann-Straussler-Scheinker syndrome, familial amyloid nephropathy with urticaria and deafness (Muckle-Wells syndrome), isolated atrial amyloid, hemodialysis-associated amyloidosis (HAA), sporadic cerebral amyloid angiopathy, hereditary cerebral amyloid angiopathy, Downs syndrome, Parkinson-dementia of Guam, age-related asymptomatic amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Kuru, Creutzfeldt-Jacob's disease, Parkinson's Disease, Huntington's chorea, and Alzheimer's disease.